Year: 2025
Type: article
Abstract: Focal Adhesion Kinase (FAK) plays dual roles in tumor progression through both kinase and scaffolding functions.While eight kinase-selective inhibitors have entered clinical trials, their inability to disrupt scaffolding domains has limited clinical success.In this issue, Zhang and Rao (DOI: 10.1021/ acsmedchemlett.5c00184)highlight recent advances in PRO-TAC-based FAK degraders that eliminate both functions.BSJ-04-146 and B5 represent promising candidates that demonstrated potent FAK degradation, migration inhibition, and improved pharmacokinetics.Early clinical outcomes of ifebemtinib (a kinase inhibitor) in combination with KRAS G12C inhibitor garsorasib showed a 90.3% ORR in NSCLC patients.These results underscore the therapeutic potential of FAK-targeting degraders and combination regimens in addressing tumor malignancy and resistance mechanisms.
Source: ACS Medicinal Chemistry Letters
Author: Simone V. Bigi-Botterill
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4411248972